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Genetic risk factors for autism-spectrum disorders: a systematic review based on systematic reviews and meta-analysis.

  • Academic Journal
  • Wei H; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, China.
    Zhu Y; Center for Disease Control and Prevention, Jianggan District, Hangzhou, 310000, China.
    Wang T; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, China.
    Zhang X; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, China.
    Zhang K; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, China.
    Zhang Z; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, China.
  • Journal of neural transmission (Vienna, Austria : 1996) [J Neural Transm (Vienna)] 2021 Jun; Vol. 128 (6), pp. 717-734. Date of Electronic Publication: 2021 Jun 11.
  • English
  • Background: Based on recent evidence, more than 200 susceptibility genes have been identified to be associated with autism until now. Correspondingly, cytogenetic abnormalities have been reported for almost every chromosome. While the results of multiple genes associated with risk factors for autism are still incomplete, this paper systematically reviews published meta-analyses and systematic reviews of evidence related to autism occurrence.
    Method: Literature search was conducted in the PubMed system, and the publication dates were limited between January 2000 and July 2020. We included a meta-analysis and systematic review that assessed the impact of related gene variants on the development of autism. After screening, this comprehensive literature search identified 31 meta-analyses and ten systematic reviews. We arranged the genes related to autism in the published studies according to the order of the chromosomes, and based on the results of a meta-analysis and systematic review, we selected 6 candidate genes related to ASD, namely MTHFR C677T, SLC25A12, OXTR, RELN, 5-HTTLPR, SHANK, including basic features and functions. In addition to these typical genes, we have also listed candidate genes that may exist on almost every chromosome that are related to autism.
    Results: We found that the results of several literature reviews included in this study showed that the MTHFR C667T variant was a risk factor for the occurrence of ASD, and the results were consistent. The results of studies on SLC25A12 variation (rs2056202 and rs2292813) and ASD risk were inconsistent but statistically significant. No association of 5-HTTLPR was found with autism, but when subgroup analysis was performed according to ethnicity, the association was statistically significant. RELN variants (rs362691 and rs736707) were consistent with ASD risk studies, but some of the results were not statistically significant.
    Conclusion: This review summarized the well-known ASD candidate genes and listed some new genes that need further study in larger sample sets to improve our understanding of the genetic basis of ASD, but sample size and heterogeneity remain major limiting factors in some genome-wide association studies. We also found that common genetic variants in some genes may be co-risk factors for autism or other neuropsychiatric disorders when we collated these results. It is worth considering screening for these mutations in clinical applications.
Additional Information
Publisher: Springer-Verlag Country of Publication: Austria NLM ID: 9702341 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-1463 (Electronic) Linking ISSN: 03009564 NLM ISO Abbreviation: J Neural Transm (Vienna) Subsets: MEDLINE
Original Publication: Wien ; New York : Springer-Verlag, 1996-
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No. 81973064 National Natural Science Foundation of China; No.KJ2017A184 Natural Science Fund of Education Department of Anhui province
Keywords: 5-HTTLPR; Autism spectrum disorders; Environment; Genetic; Gene–environment interaction; MTHFR C677T; OXTR; RELN; SHANK; SLC25A12
0 (Reelin Protein)
EC (Methylenetetrahydrofolate Reductase (NADPH2))
EC 3.4.21.- (RELN protein, human)
Date Created: 20210611 Date Completed: 20211015 Latest Revision: 20220531